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Genomic instability in radial growth phase melanoma cell lines after ultraviolet irradiation

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¹ Department of Pathology, Faculty of Medicine, Assuit University, Assuit, Egypt
² Brown Medical School, Providence, RI 02912, USA
³ Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA
⁴ Department of Dermatology, University of Wisconsin and William S Middleton Memorial Veteran Hospital, Madison, WI 53705, USA

Correspondence to:
Dr M R Hussein
Department of Pathology, Assiut University Hospitals, Assiut, Egypt; mrh17{at}swissinfo.org Background/Aims: Although ultraviolet (UV) irradiation, apoptosis, and genomic instability are all potentially involved in the pathogenesis of melanoma, in vitro studies investigating these changes in the radial growth phase of this neoplasm are still lacking; therefore, this study was designed to investigate these changes.

Method: An in vitro system consisting of three radial growth phase Wistar melanoma cell lines (WM35, WM3211, and WM1650) was established. Cells were UV irradiated (10 mJ/cm² for UVB and 6 J/cm² for UVA), harvested after UV exposure, and evaluated for viability and apoptosis using Trypan blue and terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labelling assays, respectively. Polymerase chain reaction based microsatellite assays were used to examine the cell lines for the presence of microsatellite instability (MSI) using 21 markers at the 1p, 2p, 3p, 4q, 9p, and 17p regions.

Results: Exposure to UV initiated progressive cell death associated with pronounced apoptosis, with UVA having a greater effect than UVB. MSI was found in UVB (WM35 and WM3211) and UVA (WM35) irradiated cell lines at 1p, 9p, and 17p, but not in non-irradiated cells. The prevalence of MSI was higher after UVB irradiation (14%) than UVA irradiation (4.7%), and was most frequently found at D1S233.

Conclusions: The ability of erythemogenic UV irradiation to induce both apoptosis and MSI in radial growth phase melanoma cells is suggestive of its role in melanoma pathogenesis. This instability may reflect a hypermutability state, oxidative stress induced DNA damage, replication infidelity, or a combination of these factors.

Abbreviations: CMM, cutaneous malignant melanoma; LOH, loss of heterozygosity; MED, minimal erythema dose; MSI, microsatellite instability; MSI-H/L, high/low microsatellite instability; PCR, polymerase chain reaction; TUNEL, terminal deoxynucleotidyl transferase mediated dUTP digoxigenin nick end labelling; UVA/B, ultraviolet A/B; UVR, ultraviolet irradiation; WM, Wistar melanoma

Keywords: Wistar melanoma cell lines; microsatellite instability; apoptosis; ultraviolet irradiation; radial growth phase

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